Preparation of amino carboxylic acids and their salts



Patented Sept. 18, 1945 PREPARATION OF AMINO CARBOXYLIG ACIDS AND THEIRSALTS George 0. Game, Jr., White Plains, N. Y., and

Henry C.

Chitwood and Jared W.

k, Charleston, W. Va., assignors to Carbide and Carbon Chemicals Corp.,a corporation of New York No Drawing. Original application December 20,

1941, Serial No. 423,756. Divided and this application December 23,1944, Serial No. 569,626

9 Claims.

The conversion of alcohols to the alkali metal salts of theircorresponding carboxylic acids by heating the alcohols with alkalimetals or alkali metal hydroxides has been known since the work of Dumasand Stas (Ann., 35, 129-173, 1840). Many variations and specialadaptations of this reaction have since been investigated, but themethod has not heretofore been known to be aplicable to those alcoholswhich contain functional groups which are readily attacked by strongalkalies or which are easily oxidized. The amino alcohols are of thistype, and it is well known that amino groups in general are themselvesstrongly reactive and susceptible to attack both by alkalies and inoxidizing reactions.

These known propensities of the amino compounds apparently haveexcluded, at least to the present, the amino alcohols from the class ofalcohols known to be useful in the reaction of Dumas and Stas.

The present invention is based on the unexpected discovery that aminoalcohols can be subjected to alkaline oxidation with the resultantformation of the alkali metal salts of the corresponding aminocarboxylic acids, and that this can be accomplished under manyconditions without serious attack on the amino groups. The advantagesand value of the invention will be apparent.

The process of the invention proceeds with the liberation of hydrogenaccording to the following scheme, in which the formation of thepotassium salt of amino acetic acid (glycine) is shown for illustration:

nmcmomonncon amino ethyl Potassium amino alcohol acetic acid Thisinvention can be applied to the oxidation of monoamino monohydricalcohols, to the oxidation of monoamino polyhydric alcohols and ofpolyamino polyhydric alcohols. By amino," polyamino, amino carboxylicacids, and similar terms employed in this description and in theappended claims, there is meant not only those compounds containing theamino group, NH2, but also those in which the nitrogen atom i attachedto two or three carbon atoms, as in monoor dialkylated amino alcoholsand in the dialkanoland trialkanol-amines. Also, it is to be understoodthat when alcohols, amino alcohols and similar terms are mentioned, thealcohol groups referred to for the purposes of this invention areprimary groups, that is, the OH groups are attached to terminal carbonatoms.

In addition to the oxidation of amino ethyl alcohol, as illustratedabove, this process can be applied to the formation of salts of variousother amino carboxylic acids by analogous reactions, and the aminoalcohols oxidized may contain alkyl, aryl or aralkyl groups, orcombinations of these. The hydroxides of sodium and potassium are thealkalies most conveniently useful for the practice of the invention, butequivalent strong alkalies can be used. Where both sodium and potassiumhydroxides are equally soluble in the amino alcohol undergoing reaction,there is usually little or no diilerence in the chemical action of thesein the process. The free amino carboxylic acids may be formed from thealkali metal salts initially obtained by reaction of these with variousacids. In this respect, the present invention does not differ from thepreviously known conversion or the salts of carboxylic acids generallyto the free acids, and mineral or organic acids may be used for thepurpose.

The oxidation of these amino alcohols by heating in the presence ofcaustic alkalies requires the observation of various precautions whichare unnecessary in the case of the simple alcohols. The more importantor these include, in the case of amino alcohols containing a nitrogenatom attached to only one or two carbon atoms, the avoidance of water insubstantial amounts during the reaction, since its presence seems topromote attack of the primary and secondary amino groups, and, ingeneral, the avoidance of high temperatures in the heating because 01'the tendency toward thermal instability of many of the amino carboxylicacids and their salts. The oxidation of amino alcohols in which thenitrogen is attached to three carbon atoms seems to be influenced muchless adversely by the presence of water than oxidations of aminoalcohols containing primary or secondary amino groups.

The process will be illustrated by the following examples:

Example I.Glycine A mixture of 61 gram (1 mol) of monoethanolamine and112 grams of 85% potassium hydrox ide (1.? mols) was placed in a steelreaction vessel equipped with a reflux condenser and heated by anoil-bath. The gas evolved was passed through a water scrubber to removeany ethanolamine carried by it and was then measured. This mixturewasheated for hours at an oilbath temperature of 210 C., and the crudeproduct was then washed from the reaction vessel with water. The gasevolved, which was virtually pure hydrogen, was 42.7 liters. .To theaqueous solution of crude product were added 80 grams of acetic acid andthe whole was then evaporated to dryness.

The dry residue was dissolved in 50 grams of water, after which 30 gramsof acetic acid and 200 grams of methyl alcohol were added to thissolution. A precipitate formed which was removed, and which was found tobe 19 grams of potassium oxalate. 011 adding additional methyl alcohol,amounting to a total of 1050 grams, a crystalline solid precipitated.This material was found on analysis to contain 69.2% glycine. The yieldsof products obtained amounted to 34.9% glycine and 10.3% ethanolaminerecovered was 23.5%

In a second experiment conducted in the same way using the same amountsof.materials, the reaction was continued for 32 hours with an oil-bathtemperature of 230 C. The gas evolved was 44.8 liters. The yield ofglycine obtained was 33% and that of potassium oxalate was 12.0%.

Another experiment was carried out as described above using the sameamounts of materials and a reaction period of 13 hours with an oil-bathtemperature of 240 C. The gas evolved amounted to 45.6 liters, and theyields were 32.2% of glycine and 11.0% of potassium oxalate.

Sodium hydroxide could not be used in this reaction with any markeddegree of success because it was not sufficiently soluble in theethanolamine. While aqueous solutions of sodium hydroxide formed asolution with monoethanolamine, the presence of water promoted attack ofthe amino group to such an extent as to render this form of the processundesirable for most practical purposes.

This adverse effect of water was illustrated by an experiment in which18 grams (1 mol) of water were added to the same reactants in the samequantities as set out above. The reaction was carried out as describedfor a period of 33 hours with an oil-bath temperature of 240 C. Although42.9 liters of gas were evolved, the

.yield of glycine was only 3.3% and the yield of potassium oxalate was16.1%.

Example II.-Tet1'acarboxymethyl ethylene diamine and 198 grams-of 85%potassium hydroxide (3.0 mols) was placed in a. steel reaction vesselconnected to a meter for the measurement of evolved gas. This reactionvessel was heated in an oilbath maintained within the range of 230 .to260 C. at which temperatures the evolution of gas was brisk. The extentof the reaction was followed by periodic titration of samples todetermine the calcium ion sequestration power of the product incomparison with that of the sodium salt of tetracarboxymethyl ethylenediamine of known purity.

After 14 hours of reaction the gas evolved amounted to 55 liters, whichby analysis, was found to be essentially pure hydrogen. At this point,titration indicated that the reaction mixture contained 12.8% by weightof tetrapotassium carboxymethyl ethylene diamine or its equivalent incalcium sequestering power. After 17 hours reaction, the gas evolvedmeasured 66 liters and potassium oxalate. The

the content of tetrapotassium carboxymethyl ethylene diamine was 17.5%by weight. From this point, continuation of the reaction resulted in adecrease of the content of the salt in the product.

Aqueous solutions of the tetrapotassium carboxymethyl ethylene diaminesalt obtained may be treated with an excess of strong mineral acid, suchas sulfuric or hydrochloric acids, to set free amino acid, when pure,has a low solubility in cold water, in contrast to the ready solubilityof its alkali metal salts.

A reaction was carried out exactly as described in Example II exceptthat 126 grams of 95% sodium hydroxide (3.0 mols) replaced the potassiumhydroxide. The reactants were heated at an oil-bath temperature of 250to 285 C. After 15 hours, the gas evolved, mainly hydrogen,

.measured 35 liters, and 15% by weight of the reaction mixture wasdetermined by titration to be tetrasodium carboxymethyl ethylenediamine. Further heating appeared neither, to increase greatly the totalvolume of gas evolved nor to increase materially the yield of product.

Example IV. Tetras0dium carboxymethyl ethylene diamine A similarreaction was carried out in which the tetraethanol ethylene diamine washeated with an excess of a 30% aqueous solution of sodium hydroxide atan oil-bath temperature of about 275 C.

The reaction mixture showed a calcium sequestering power indicatingabout 12% of the theoretical yield of tetrasodium carboxymethl ethylenediamine; In this case, the amino groups are tertiary, and comparisonwith the yield obtained in Example II indicates that the deleteriouseffect of water was much less noticeable. than in the oxidation of theprimaryethanolamine.

In the oxidations described in Examples 11, I11 and IV, the reaction wasnot found to proceed to any significant extent'at temperatures muchlower than 250 C. The high temperatures required were accompanied bysome decomposition of the products, and this makes their preparation inhigher yields quite difficult.

Example V. Tripotas sium carboxymethylamine A mixture of 149 grams (1mol) of triethanolamine, 224 grams (4.0 mols) of potassium hydroxide and40 grams of water was placed in a steel reaction vessel as described inExample II.

- this invention depends on the amino alcohol to be oxidized and on thestrength of the alkali used. It has been found that the reaction can becarried out at lower temperatures and with greater facility by the aidof'certain metals or their compounds as catalysts, and this improvementin the process is the subject of copending application Serial No.457,515, filed September This.

5, 1942, by H. C. Chitwood. The common method of operation is to mix thereactants and heat them until a substantial evolution of hydrogen occursas evidenced either by its escape through the vent of the reactionvessel, or by an increase in pressure if a closed system is used. Thetemperature then is either held at this point or slowly increased toattain the desired rate of reaction. The completion of the reaction isindicated when the rate of hydrogen evolution becomes very slight, atwhich time approximately a theoretical amount of gas will have beenfound to have been given oil. The operating pressure is of slightimportance except to prevent evaporation of the liquids present. When ahigh-boiling amino alcohol and very little water are used, as in thepreparation of glycine from monoethanolamine, the reaction ay beconveniently carried out at atmospheric p essure using a refluxcondenser to return an y volatilized liquid. With low-boiling aminoalcohols, or when substantial amounts of water are resent in thereaction, operation under pressure is preferred and this can beconveniently done by applying gas pressure to the reaction system. Usingaqueous solutions of ducted in a closed vessel and a pressure of about300 pounds per square 1 ch of hydrogen or an inert gas is applied to thesystem. This pressure can be maintained at about 300 pounds per squareinch or higher by regulating the rate of gas removal, or it can bepermitted to build up throughout the reaction as desired. Increasedhydrogen pressure up to 1500 pounds per square inch or more apparentlyhas no noticeable effect on the yield of product.

In addition to the reactions illustrated by the foregoing examples, thisprocess has been emloyed to form amino carboxylic acids and their alkalimetal'salts from a wide variety of other amino alcohols, among which arethe following: tetracarboxymethyl propylene diamine from tetraethanolpropylene diamine; pentacarboxymethyl diethylene triamine frompentaethanol diethylene triamine; hexacarboxymethyl triethylenetetramine from hexaethanol triethylene tetramine; dicanboxymethylaminefrom diethanolamine; and isopropyl and butyl dicarboxymethylamines fromthe corresponding isopropyl and butyl diethanolamines.

'the alkali, the reaction iinmost conveniently con- This applicationwhich relates to a process for making the alkali metal salts of primaryamino and secondary amino carboxylic acids is a division of applicationSerial No. 423,756, filed December 20, 1941, which relates to a processfor making the alkali metal salts of tertiary amino carboxylic acids.

Many modifications and variations of the process will be apparent tothose skilled in the art and these are included within the scope of theinvention as defined by the appended claims.

We claim:

1. A process for making an alkali metal salt of an amino carboxylic acidwhich comprises heating an amino alcohol of the group consisting ofprimary amino and secondary amino a1- cohols containing at least oneprimary alcohol group with an alkali metal hydroxide soluble therein andhaving a concentration, based on the weight of alkali metal hydroxideand water present therewith, of not less than 85 per cent, at atemperature at which hydrogen is liberated from the reaction mixture,with formation of the corresponding amino carboxylic acid alkali metalSalt.

2. A process for making an alkali metal salt or an amino carboxylic acidwhich comprises heating an amino alcohol of the group consisting ofprimary amino and secondary amino alcohols containing at least oneprimary alcohol group with an alkali metal hydroxide soluble therein andhaving a concentration, based on the weight of alkali metal hydroxideand water present therewith, of not less than per cent, at a temperatureat which hydrogen is liberated from the reaction mixture and notsubstantially higher than 285 C., with formation of the correspondingamino carboxylic acid alkali metal salt.

3. A process for making an alkali metal salt of an amino carboxylic acidwhich comprises heating an amino alcohol of the group consisting ofprimary amino and secondary amino alcohols containing at least oneprimary alcohol group with an excess of an alkali metal hydroxidesoluble therein and having a concentration, based on the weight ofalkali metal hydroxide and water present therewith, of not less than 85per cent, at a temperature at which hydrogen is liberated from thereaction mixture, with formation or the cor-responding amino carboxylicacid alkali metal sa 4. A process for making an alkali metal salt of anamino carboxylic acid which comprises heating an amino alcohol or thegroup consisting of primary amino and secondary amino alcoholscontaining at least one primary alcohol group with an alkali metalhydroxide of a molecular weight from 40 to 56.1 soluble therein andhaving a concentration, based on the weight of the alkali metalhydroxide and water present therewith, of not .less than 85 per cent, ata temperature at which hydrogen is liberated from the reaction mixture,with formation of the corresponding amino carboxylic acid salt.

5. A process for making an alkali metal salt of an amino carboxylic acidwhich comprises heating an amino alcohol of the group consisting ofprimary amino and secondary amino alcohols containing at least oneprimary alcohol group with an alkali metal hydroxide of a molecularweight from 40 to 56.1 soluble therein and having a concentration, basedon the weight of alkali metal hydroxide and water present therewith, ofnot less than 85 per cent, at a temperature at which hydrogen isliberated from the reaction mixture and not substantially higher than285 C., with formation of the corresponding amino carboxylic acid salt.

6. A process for making an alkali metal salt of a primary aminocarboxylic acid which comprises heating a primary amino alcohol having aprimary alcohol group with an alkali metal hydroxide soluble therein andhaving a concentration, based on the weight of alkali metal hydroxideand water present therewith, of not less than 85 per cent, at atemperature at which hydrogen is liberated from the reaction mixture,with formation of the corresponding primary amino car boxylic acidalkali metal salt.

'7. A process for making an alkali metal salt of a primary aminocarboxylic acid which comprises heating a primary amino alcohol having aprimary alcohol group with potassium hydroxide having a concentration,based on the weight of potassium hydroxide and water present therewith,of not less than 85 per cent, at a temperature at which hydrogen isliberated from the reaction mixture, with formation of the correspondingprimary amino carboxylic acid alkali metal salt.

8. A process for making the potassium salt of glycine which comprisesheating monoethanolamine with potassium hydroxide having aconcentration, based on the weight of the potassium hydroxide and waterpresent therewith, of not less than 85 per cent, at a temperature atwhich hydrogen is liberated from the reaction mixture, with formation ofthe glycine potassium salt.

9. A process for making an alkali metal salt of glycine which comprisesheating monoethanolm amine with potassium hydroxide having aconcentration, based on the weight of the potassium hydroxide and waterpresent therewith, of not less than about 85 per cent. at a temperatureat which hydrogen is liberated from the reaction mixture and notsubstantially above 240 C., with formation of the glycine potassiumsalt.

GEORGE 0. CURME, JR. HENRY C. CHI'I'WOOD. JARED W. CLARK.

